The present invention relates to a process for preparing sugammadex sodium, a modified gamma cyclodextrin chemically designated as 6A,6B,6C,6D,6E,6F,6G,6H-Octakis-S-(2-carboxyethyl)-6A,6B,6C,6D,6E,6F,6G,6H-octathio-γ-cyclodextrin sodium salt (1:8) with a molecular weight of 2178.01 and a formula as shown below:

Sugammadex sodium (marked as BRIDION®) is a modified gamma cyclodextrin. It forms a complex with neuromuscular blocking agents rocuronium and vecuronium, and it reduces the amount of neuromuscular blocking agent available to bind to nicotinic cholinergic receptors in the neuromuscular junction. This results in reversal of neuromuscular blockade induced by rocuronium and vecuronium. BRIDION® was approved by the U.S. Food and Drug Administration (FDA) on Dec. 15, 2015.
U.S. Pat. No. RE 44,733 (the '733 patent) describes a preparation method of sugammadax as shown in Scheme 1 below:

Sugammadex is prepared by dissolving γ-cyclodextrin in X2 (Cl2 or Br2)/PPh3/NaOMe in DMF followed by adding NaH and 3-mercapto propionic acid or NaOH/Cs2CO3/3-mercapto propionic acid.
A similar approach for sugammadax preparation is reported in U.S. Pat. No. 9,120,876B2 (the '876 patent, Scheme 2 below). Sugammadex is prepared by dissolving γ-cyclodextrin in PX3 or PX5 in DMF followed by adding NaH and 3-mercapto propionic acid. Based on the '733 patent and the '876 patent, PPh3 is used to produce the intermediate, and a significant amount of side product PPh3O2 is produced. PPh3O2 is hard to remove, and the intermediate is hard to isolate.

Another synthetic route is reported in Chinese Patent Application CN105273095A (Scheme 3 below). Sugammadex is prepared by dissolving γ-cyclodextrin in oxalyl chloride or SOCl2 in DMF followed by adding NaH and 3-mercapto propionic acid. When oxalyl chloride or SOCl2 is added into the mixture, exothermic heat and HCl are produced.

Bull Soc Chim Fr 1995 132 857-866 discloses that halide-γ-cyclodextrin can be prepared by reacting γ-cyclodextrin with MsCl in DMF.

In view of the above, there remains a need for the development of improved processes for the preparation of sugammadax sodium.